Rasmussen's syndrome (RS) is a rare neurodegenerative disease of childhood in which a single cerebral hemisphere undergoes progressive destruction. The disease is characterized by gradual loss of functions sub-served by the involved hemisphere as well as severe epileptic seizures. During the current funding period, study of an animal model of RS and of brain tissue excised from children with RS provided evidence that inappropriate activation of complement may contribute to the disease. In particular, immunocytochemical evidence of membrane attack complex formation on neurons in RS brains was obtained. Despite evidence of membrane attack complex immunoreactivity in RS brains and in several neurodegenerative diseases including Alzheimer's, whether inappropriate activation of complement in mammalian brain exerts any deleterious effects is unknown. We have obtained preliminary evidence that inappropriate activation of complement, in particular the membrane attack complex, produces seizures and cell death in rats in vivo. The objective of this proposal is to investigate a series of hypotheses related to the pathological consequences of activation of the membrane attack complex in the cortex of mammalian brain. Parallel investigations will be performed in awake, freely moving rats in vivo and in organotypic explant cultures of rat hippocampus and in primary cultures of embryonic rat cortical cells in vitro.